This invention relates to a reduction of the occurence of intimal hyperplasia which can occur when autogeneous artery, vein, biologic or synthetic conduits are grafted in aorto-coronary, femoral-distal or any other bypass grafts of the body with distal end-to-side anastomosis. End-to-side anastomosis is preferred to end-to-end anastomosis in humans so that back perfusion to vital structures can be maintained. Although influenced by shear stress, turbulent flow and the compliance mismatch of the graft and host artery, this anastomosis configuration is performed out of necessity.
Human occluded femoral distal bypass grafts (Dacron.RTM. 7, PTFE-27, bovine-4, and vein graft-11, obtained from the Northwestern University, University of Michigan and Louisiana State University), removed at the time of the lower extremity revascularization, were studied. Distal anastomotic intimal hyperplasia was found to occur exclusively at the heel and the toe of the distal anastomosis and the floor of the host artery. Histocytologic analysis of the distal anastomotic intimal hyperplasia (DAIH) revealed an interlamination of smooth muscle cells and extracellular matrix. A similar morphologic architecture of the distal anastomotic intimal hyperplasia occurred in different types of grafts as reported in Intimal Hyperplasia and Neointima: An Ultrastructural Analysis of Thrombosed Grafts in Humans, Surg. 93:809-817, Sottiurai, V. S., Yao, J. S. T., et. al. Two forms of pathomorphogenesis were recognized in DAIH. Transformation of smooth muscle cells to myofibroblasts induced medial fibroplasia, whereas degeneration of smooth muscle cells progressed to medial necrosis. Smooth muscle cells seemed to play a role not previously recognized in the pathogenesis of the extracellular matrix leading to DAIH and graft occlusion.
Similar to human distal bypass grafts, DAIH in canine polytetrafluoroethylene (PTFE) grafts (n-42) in experimental studies occurred exclusively at the heel and the toe of the graft and the floor of the host artery (P&gt;0.001). Light microscopy and transmission electron microscopy (TEM) revealed the existence of a similar architecture of interlamination of cellular elements and extracellular matrix in DAIH. TEM further documented a gradual cell transformation and orientation from the graft to the lumen. The former was characterized by a gradual reduction of rough endoplasmic reticula with a concomitant acquisition of myofilaments, transforming ovoid mesenchymoid cells to slender myofibroblasts. The orientation of cells in DAIH was characterized by a random cell distribution at the periphery and a well organized interlamination of myofibroblasts with extracellular matrix near the lumen. DAIH is a biologic entity with active cellular and subcellular events. The biogenesis of DAIH appears to be influenced by the hemodynamics of blood flow at the distal anastomosis. See Distal Anastomotic Intimal Hyperplasia in Human and Canine Bypass Grafts: An Ultrastructural Analysis, J. Vasc. Surg. submitted for publication, Sottiurai, V. S., Batson, R. C., et al. One hundred and twenty ilio-distal bypasses were performed in dogs using standard (n-30) and thin wall (n-90) PTFE grafts. Fifty percent of the distal anastomoses had a Linton vein patch angioplasty to alter the compliance mismatch between a graft and the artery. Long-term follow-up (1-12 months) showed DAIH occuring at the heel and the toe of the distal anastomosis and the floor of the host artery. Vein patch angioplasty allegedly reduced the compliance mismatch at the distal anastomosis in standard PTFE graft and improved the patency rate by 60% over the standard PTFE graft without a distal vein patch angioplasty. Conversely, thin wall PTFE graft that has compliance comparable to dissected artery (scar tissue surrounding a dissected artery is known to reduce the compliance of the vessel) had a better patency rate (51%) than thin wall PTFE graft with a distal vein patch angioplasty. See The Role of Vein Patch at Distal Anastomosis, presented at the Southern Association for Vascular Surgery, Jan. 1986, Sottiurai, V. S., et al., submitted for publication.
Compliant differences between the PTFE graft and artery can present technical difficulty in small vessel anastomosis, as well as being implicated in late development of distal anastomotic intimal hyperplasia (DAIH). A distal autogenous vein patch permits precise suturing of the distal anastomosis and minimizes technical difficulty leading to early graft failure. Improvement of compliance mismatch of the PTFE graft and artery may impede the unwelcomed development of DAIH. The adjunctive use of a distal vein patch has resulted in excellent immediate graft patency in humans. See Linton Patch Angioplasty: An adjunct to Distal Bypass with Polytetrafluoroethylene Grafts, Ann. Surg. 199:684-1984, Batson, R. C., Sottiurai, V. S., et al.
Despite the absence of compliance mismatch in transpubic autogenous femoral-femoral bypass (n-20) with an end-to-side distal anastomosis and femoral interposition graft (n-20) with a distal end-to-end anastomosis, DAIH still occurred at the end-to-side anastomosis (100%) without graft occlusion and none at the end-to-end anastomosis (P&gt;0.001). Results of this experiment strongly suggested that, although prevention of compliance mismatch at the distal anastomosis would reduce the magnitude of DAIH formation, it could not prevent its occurrence. It is believed that the unanatomic and unphysiologic end-to-side distal anastomosis (an unnatural occurrence in primate vasculature) is responsible for the alteration of hemodynamics of blood flow at the distal anastomosis and for the occurrence of flow separation at the heel and the toe of the graft. The reverberation of blood flow and flow separation cause endothelial injury and allow the subendothelial smooth muscle cells to be influenced of leukocytes, monocytes and platelets. The latter two blood-borne substances are known to enhance smooth muscle cell migration, proliferation and extracellular matrix production which results in DAIH formation. See Distal Anastomotic Intimal Hyperplasia: Biogenesis and Etiology, presented at the Southern Association for Vascular Surgery, Jan. 1987, Sottiurai, V. S. et al., submitted for publication.